Congratulations to Ms Cai Wanpei, a PhD student from Dr Alan Prem Kumar’s group for receiving the prestigious Avon-AACR International Scholar-in-Training Travel Award in the amount USD$2,000 to attend and present her PhD work at the above conference. Her abstract was chosen for this award because the work is highly rated by the Abstract Selection Committee.
DEAD-box RNA helicase DP103 as a Novel Regulator of Wnt/β-catenin Signaling Pathway and Promotes Cancer Stem Cell-like Behavior in Triple Negative Breast Cancers
Wanpei Cai1,2, Jit Kong Cheong5, Edison5, Arindam Banerjee1,8, Tuan Zea Tan1, Einas M. Yousef9, Louis Gaboury9, Jean Paul Thiery1,3, Peter E. Lobie1,2, David M. Virshup3,5, Celestial T. Yap4, Alan Prem Kumar1,2,6,7
1Cancer Science Institute of Singapore, National University of Singapore; Departments of 2Pharmacology and 3Biochemistry, 4Physiology Yong Loo Lin School of Medicine, National University of Singapore; 5Cancer & Stem Cell Biology Program, Graduate Medical School, Duke-NUS; 6School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, Western Australia; 7Department of Biological Sciences, University of North Texas, Denton, TX, USA; 8Somers Cancer Research Building, Cancer Research UK Centre, Faculty of Medicine, University of Southampton; 9Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal
Despite recent advances in breast cancer therapeutics, mortality of metastatic triple negative breast cancer (TNBC) subtype remains high; due to their lack of hormone receptors expression for targeted therapy. Aberrant activation of Wnt/β-catenin signaling has been associated with breast cancers; where 40% of total breast cancers have elevated β-catenin levels with increased Wnt activity. Recently, we identified DEAD-box RNA helicase DP103 as a novel prognostic biomarker and metastasis-driving oncogene; highly expressed in TNBC subtype. Interestingly, we found high DP103 expression to be positively correlated with high β-catenin expression in clinical specimens (n=400). This led us to hypothesize a possible role of DP103 in modulating the Wnt/β-catenin pathway in TNBCs. Depletion of DP103 in metastatic TNBC cells decreases Wnt/β-catenin activity and expression of downstream Wnt target genes, while overexpression of DP103 increases Wnt activity. Depletion of DP103 also decreases phosphorylation of LRP6 and several important Wnt modulators required for downstream Wnt activation. Moreover, induction of Wnt/β-catenin signaling in Wnt responsive TNBC cells also significantly increased DP103 expression, indicating a possible positive feedback loop. Both canonical and non-canonical Wnt signaling is known to independently promote stem cell growth in mammospheres. Herein, we will also provide evidence on the role of DP103 in promoting breast cancer stem cell-like properties. Collectively, our data show a novel regulatory role of DP103 in the Wnt/β-catenin signaling pathway and in promoting breast cancer stem cell-like behavior, presenting itself as a potential drug target in TNBC patients.